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| Gene | KIT |
| Variant | D820G |
| Impact List | missense |
| Protein Effect | unknown |
| Gene Variant Descriptions | KIT D820G lies within the protein kinase domain of the Kit protein (UniProt.org). D820G has been associated with tyrosine kinase inhibitor resistance (PMID: 18488160), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Nov 2025). |
| Associated Drug Resistance | Y |
| Category Variants Paths |
KIT mutant KIT exon17 KIT D820G |
| Transcript | NM_000222.3 |
| gDNA | chr4:g.54733167A>G |
| cDNA | c.2459A>G |
| Protein | p.D820G |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_001385290.1 | chr4:g.54733167A>G | c.2459A>G | p.D820G | RefSeq | GRCh38/hg38 |
| NM_000222.3 | chr4:g.54733167A>G | c.2459A>G | p.D820G | RefSeq | GRCh38/hg38 |
| NM_000222.2 | chr4:g.54733167A>G | c.2459A>G | p.D820G | RefSeq | GRCh38/hg38 |
| XM_005265741 | chr4:g.54733167A>G | c.2459A>G | p.D820G | RefSeq | GRCh38/hg38 |
| XM_005265741.1 | chr4:g.54733167A>G | c.2459A>G | p.D820G | RefSeq | GRCh38/hg38 |
| NM_000222 | chr4:g.54733167A>G | c.2459A>G | p.D820G | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| KIT W557_K558del KIT D820G | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 |
| KIT W557_K558del KIT D820G | Advanced Solid Tumor | resistant | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were resistant to Sutent (sunitinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 |
| KIT W557_K558del KIT D820G | Advanced Solid Tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 |
| KIT W557_K558del KIT D820G | Advanced Solid Tumor | resistant | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). | 25239608 |
| KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, a gastrointestinal stromal tumor patient-derived xenograft (PDX) model harboring KIT P577del, KIT W557Lfs*5, and KIT D820G demonstrated resistance to treatment with Gleevec (imatinib) (PMID: 27777285). | 27777285 |
| KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | sensitive | Cabozantinib | Preclinical - Pdx | Actionable | In a preclinical study, Cometriq (Cabometyx, cabozantinib) slowed tumor growth and decreased mitotic activity in a gastrointestinal stromal tumor patient-derived xenograft (PDX) model harboring KIT P577del, KIT W557Lfs*5, and KIT D820G (PMID: 27777285). | 27777285 |
| KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | sensitive | PLX9486 | Preclinical - Pdx | Actionable | In a preclinical study, PLX9486 treatment decreased Mapk phosphorylation and Kit downstream signaling, inhibited proliferation, and reduced tumor growth in a Gleevec (imatinib)-resistant patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT P577del, W557Lfs*5, and D820G (PMID: 30523507). | 30523507 |
| KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient derived xenograft (PDX) model with a gastrointestinal stromal tumor harboring KIT W557Lfs*5, KIT P577del, and KIT D820G was sensitive to treatment with Ayvakit (avapritinib), demonstrating a stabilized tumor volume at a dose of 10mg/kg and 27% tumor regression at a dose of 30mg/kg, a histologic response, and apoptotic activity (PMID: 30274985). | 30274985 |
| KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | predicted - sensitive | IDRX-42 | Preclinical - Pdx | Actionable | In a preclinical study, IDRX-42 treatment inhibited mitosis and decreased tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT P577del, W557Lfs*5, and D820G (PMID: 37223931). | 37223931 |
| KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | predicted - sensitive | Dovitinib | Preclinical - Pdx | Actionable | In preclinical study, Dovitinib (TKI258) treatment stabilized tumor volume in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT P577del, KIT W557Lfs*5, and KIT D820G (PMID: 35625872). | 35625872 |
| KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | predicted - sensitive | Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, Sutent (sunitinib) treatment did not inhibit Kit downstream signaling, however, delayed tumor growth and induced histologic response in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT P577del, W557Lfs*5, and D820G (PMID: 25132955). | 25132955 |
| KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Stivarga (regorafenib) treatment decreased Kit activation and downstream signaling, decreased tumor volume to 70% of original size, and induced histologic response in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT P577del, W557Lfs*5, and D820G (PMID: 25132955). | 25132955 |
| KIT V559D KIT D820G | Advanced Solid Tumor | sensitive | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D820G and KIT V559D were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation (PMID: 24205792). | 24205792 |
| KIT V555_L576del KIT D820G KIT D820Y | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT D820G and KIT D820Y were identified as secondary mutations in a patient with gastrointestinal stromal tumor harboring a primary KIT V555_L576del mutation, who developed resistance to Gleevec (imatinib) (PMID: 18488160). | 18488160 |
| KIT exon 11 del KIT D820G | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT D820G in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... |
| KIT V560D KIT D820G KIT N822K KIT Y870* | gastrointestinal stromal tumor | predicted - resistant | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, KIT N822K and KIT D820G were identified as secondary resistance mutations in a patient with a gastrointestinal stromal tumor harboring primary KIT Y870* and V560D mutations who developed resistance to Gleevec (imatinib) and Mektovi (binimetinib) treatment (PMID: 35041493; NCT01991379). | 35041493 |